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A Phase I Study of Safety & Immunogenicity of AERAS-456 in HIV-Neg. Adults Treated for Drug-susceptible Pulmonary TB (C-037-456)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02375698
Recruitment Status : Completed
First Posted : March 3, 2015
Last Update Posted : August 25, 2017
Statens Serum Institut
Information provided by (Responsible Party):

Brief Summary:
This is a Phase I, double-blind, randomized, placebo-controlled safety and immunogenicity study in adults who have recently been successfully treated for drug-susceptible pulmonary Tuberculosis (TB). The safety and immunogenicity profile of escalating doses of AERAS-456 in HIV-negative subjects recently treated for drug-susceptible pulmonary TB will be investigated. The study will be conducted at one or more sites in South Africa.

Condition or disease Intervention/treatment Phase
Tuberculosis Biological: H56:IC31 Biological: Placebo Phase 1

Detailed Description:
This study will be the first evaluation of AERAS-456 in subjects who have completed a full course of treatment prescribed for pulmonary TB. Subjects will begin screening for study participation when they have completed 4 calendar months of TB treatment. Subjects meeting the inclusion/exclusion criteria will be randomized within a study group in a 3:1 ratio (N=18 AERAS-456; N=6 placebo) to receive two 0.5 mL intramuscular injections of AERAS-456 or placebo eight weeks apart, on Study Day 0 and Study Day 56.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: A Phase I, Double-blind, Randomized, Placebo-controlled, Study to Evaluate the Safety and Immunogenicity of AERAS-456 in HIV Negative Adults Successfully Treated for Drug-susceptible Pulmonary Tuberculosis
Actual Study Start Date : November 21, 2014
Primary Completion Date : June 24, 2016
Study Completion Date : October 24, 2016

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Gr 1 H56:IC31 5/500
5ug H56 + 500 ug IC31
Biological: H56:IC31
H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c).
Other Name: AERAS-456
Placebo Comparator: Placebo
The placebo consists of 10mM Tris and 169 mM NaCl pH 7.4.
Biological: Placebo
The placebo consists of 10mM Tris and 169 mM NaCl pH 7.4.

Primary Outcome Measures :
  1. Safety of 2 Intramuscular (IM) injections of AERAS-456 compared to 2 injections of placebo, in HIV-negative subjects who have recently completed treatment for drug-susceptible pulmonary TB and who are confirmed Mtb negative prior to vaccination. [ Time Frame: Thru Day 420 of the study ]
    • Occurrence of solicited adverse events occurring within 7 days and unsolicited adverse events occurring within 28 days after each vaccination.
    • Occurrence of serious adverse events and adverse events of special interest after the first vaccination through end of study follow-up.

Secondary Outcome Measures :
  1. Immunogenicity of 2 IM injections of AERAS-456 compared to 2 injections of placebo, in HIV-negative subjects who have recently completed treatment for drug-susceptible pulmonary TB and who are confirmed Mtb negative prior to vaccination [ Time Frame: Thru Day 224 of the study ]
    13-Color PBMC Intracellular Cytokine Staining (ICS) Assay and IFN-γ PBMC ELISpot to determine cellular immune response to study vaccine.

Other Outcome Measures:
  1. Humoral immune response to AERAS-456 [ Time Frame: Up to study day 224 ]
    Serum antigen-specific IgG (ELISA) to determine humoral immune response to study vaccine.

  2. Innate immune responses to AERAS-456 in order to identify early expression signatures that can predict immune responses [ Time Frame: Up to study day 63 ]
    RNA analysis (transcriptional profiling) to perform a multivariate analysis of the innate immune responses following vaccination in order to identify early expression signatures that can predict immune responses.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Is HIV-negative.
  2. Is male or female aged 18 through 60 years on Study Day 0.
  3. Has completed the written informed consent process.
  4. Has a diagnosis of confirmed pulmonary tuberculosis and is on standard TB treatment.
  5. Is confirmed to be Mtb negative by either 2 GeneXpert tests or 2 cultures from sputum samples taken on 2 different days at least 1 week apart, the first after at least 4 calendar months of TB treatment and the second day not later than after 5 calendar months (with a window of plus 1 week) of treatment.
  6. Agrees to complete the prescribed course of TB treatment (completion of TB treatment can occur after vaccination on Study Day 0; subject must have completed at least 5 calendar months of TB treatment on Study Day 0; if TB treatment is completed before randomization/vaccination then the time from completion of TB treatment to randomization/vaccination should not exceed 28 days).
  7. For female subjects: agrees to avoid pregnancy between screening and up until two months after last vaccination. Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses if menopausal) in sexual relationships with men must use an acceptable method of avoiding pregnancy from 28 days prior to administration of study vaccine up until two months after the last vaccination. Acceptable methods of avoiding pregnancy include a sterile sexual partner, sexual abstinence (not engaging in sexual intercourse), hormonal contraceptives (oral, injection, transdermal patch, or implant), vaginal ring, or intrauterine device (IUD).
  8. Agrees to stay in contact with the study site for the full duration of the study, providing updated contact information as necessary, and has no current plans to move from the study area during the duration of the study.

Exclusion Criteria:

  1. Evidence of a new acute illness that may compromise the safety of the subject in the study on Study Day 0.
  2. History of TB prior to current episode.
  3. TB meningitis or other forms of severe TB with high risk of a poor outcome.
  4. Previous medical history that may compromise the safety of the subject in the study, including but not limited to severe impairment of pulmonary function from tuberculosis infection or other pulmonary disease; chronic illness with signs of cardiac or renal failure; suspected progressive neurological disease; or uncontrolled epilepsy.
  5. Evidence of any systemic disease or any acute or chronic illness that may interfere with the evaluation of the safety of the vaccine.
  6. History or laboratory evidence of any possible immunodeficiency state.
  7. History of allergic disease or reactions likely to be exacerbated by any component of the study vaccine.
  8. Received any non-BCG TB vaccine previously.
  9. For female subjects: Currently pregnant, lactating/nursing, or a positive urine HCG.
  10. Severe anemia, defined as hemoglobin less than 10 g/dL or a hematocrit less than 30 percent based on screening hematology obtained within 7 days before randomization on Study Day 0.
  11. History of autoimmune disease or immunosuppression.
  12. Used immunosuppressive medication within 42 days before Study Day 0 (inhaled and topical corticosteroids are permitted).
  13. Received immunoglobulin or blood products within 42 days before Study Day 0.
  14. Received any investigational drug therapy or investigational vaccine within 6 months before Study Day 0, or planned participation in any other investigational study during the study period.
  15. Received any licensed vaccine within 28 days before Study Day 0, or receipt of any vaccine or immunomodulating agent through Study Day 63.
  16. Is, in the judgment of the principal investigator, not suitable to participate in this clinical study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02375698

South Africa
Task Clinical Research Centre
Bellville 7530, Cape Town, South Africa
University of Cape Town Lung Institute
Mowbray, Cape Town, South Africa
The Aurum Institue
Johannesburg, South Africa
Sponsors and Collaborators
Statens Serum Institut
Study Director: Dereck Tait, MBChB Aeras

Responsible Party: Aeras
ClinicalTrials.gov Identifier: NCT02375698     History of Changes
Other Study ID Numbers: C-037-456
First Posted: March 3, 2015    Key Record Dates
Last Update Posted: August 25, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections